CN102112229A - Microfluidic foil structure for metering of fluids - Google Patents

Microfluidic foil structure for metering of fluids Download PDF

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Publication number
CN102112229A
CN102112229A CN2009801303600A CN200980130360A CN102112229A CN 102112229 A CN102112229 A CN 102112229A CN 2009801303600 A CN2009801303600 A CN 2009801303600A CN 200980130360 A CN200980130360 A CN 200980130360A CN 102112229 A CN102112229 A CN 102112229A
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China
Prior art keywords
film
substrate
chamber
microfluidic structures
fluid
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Granted
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CN2009801303600A
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Chinese (zh)
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CN102112229B (en
Inventor
德克·库罗斯基
玛丽奥·亨普尔
格特·布兰肯斯滕
托比亚斯·罗登费尔斯
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Boehringer Ingelheim Microparts GmbH
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Boehringer Ingelheim Microparts GmbH
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    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C65/00—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor
    • B29C65/02—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor by heating, with or without pressure
    • B29C65/18—Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor by heating, with or without pressure using heated tools
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
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    • B29C66/01—General aspects dealing with the joint area or with the area to be joined
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    • B29C66/10—Particular design of joint configurations particular design of the joint cross-sections
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    • B29C66/01—General aspects dealing with the joint area or with the area to be joined
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    • B29C66/328—Leaving the burrs unchanged for providing particular properties to the joint, e.g. as decorative effect
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    • B29C66/00—General aspects of processes or apparatus for joining preformed parts
    • B29C66/50—General aspects of joining tubular articles; General aspects of joining long products, i.e. bars or profiled elements; General aspects of joining single elements to tubular articles, hollow articles or bars; General aspects of joining several hollow-preforms to form hollow or tubular articles
    • B29C66/51—Joining tubular articles, profiled elements or bars; Joining single elements to tubular articles, hollow articles or bars; Joining several hollow-preforms to form hollow or tubular articles
    • B29C66/53—Joining single elements to tubular articles, hollow articles or bars
    • B29C66/534—Joining single elements to open ends of tubular or hollow articles or to the ends of bars
    • B29C66/5346—Joining single elements to open ends of tubular or hollow articles or to the ends of bars said single elements being substantially flat
    • B29C66/53461—Joining single elements to open ends of tubular or hollow articles or to the ends of bars said single elements being substantially flat joining substantially flat covers and/or substantially flat bottoms to open ends of container bodies
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00—General aspects of processes or apparatus for joining preformed parts
    • B29C66/70—General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material
    • B29C66/72—General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the structure of the material of the parts to be joined
    • B29C66/723—General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the structure of the material of the parts to be joined being multi-layered
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/02—Machines, pumps, or pumping installations having flexible working members having plate-like flexible members, e.g. diaphragms
    • F04B43/04—Pumps having electric drive
    • F04B43/043—Micropumps
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0442—Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0638—Valves, specific forms thereof with moving parts membrane valves, flap valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/082—Active control of flow resistance, e.g. flow controllers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
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    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00—General aspects of processes or apparatus for joining preformed parts
    • B29C66/70—General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material
    • B29C66/71—General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the composition of the plastics material of the parts to be joined
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00—General aspects of processes or apparatus for joining preformed parts
    • B29C66/80—General aspects of machine operations or constructions and parts thereof
    • B29C66/81—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps
    • B29C66/814—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps characterised by the design of the pressing elements, e.g. of the welding jaws or clamps
    • B29C66/8141—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps characterised by the design of the pressing elements, e.g. of the welding jaws or clamps characterised by the surface geometry of the part of the pressing elements, e.g. welding jaws or clamps, coming into contact with the parts to be joined
    • B29C66/81411—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps characterised by the design of the pressing elements, e.g. of the welding jaws or clamps characterised by the surface geometry of the part of the pressing elements, e.g. welding jaws or clamps, coming into contact with the parts to be joined characterised by its cross-section, e.g. transversal or longitudinal, being non-flat
    • B29C66/81415—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps characterised by the design of the pressing elements, e.g. of the welding jaws or clamps characterised by the surface geometry of the part of the pressing elements, e.g. welding jaws or clamps, coming into contact with the parts to be joined characterised by its cross-section, e.g. transversal or longitudinal, being non-flat being bevelled
    • B29C66/81419—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps characterised by the design of the pressing elements, e.g. of the welding jaws or clamps characterised by the surface geometry of the part of the pressing elements, e.g. welding jaws or clamps, coming into contact with the parts to be joined characterised by its cross-section, e.g. transversal or longitudinal, being non-flat being bevelled and flat
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
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    • B29C66/00—General aspects of processes or apparatus for joining preformed parts
    • B29C66/80—General aspects of machine operations or constructions and parts thereof
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    • B29C66/814—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps characterised by the design of the pressing elements, e.g. of the welding jaws or clamps
    • B29C66/8141—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps characterised by the design of the pressing elements, e.g. of the welding jaws or clamps characterised by the surface geometry of the part of the pressing elements, e.g. welding jaws or clamps, coming into contact with the parts to be joined
    • B29C66/81411—General aspects of the pressing elements, i.e. the elements applying pressure on the parts to be joined in the area to be joined, e.g. the welding jaws or clamps characterised by the design of the pressing elements, e.g. of the welding jaws or clamps characterised by the surface geometry of the part of the pressing elements, e.g. welding jaws or clamps, coming into contact with the parts to be joined characterised by its cross-section, e.g. transversal or longitudinal, being non-flat
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    • B29L2031/00—Other particular articles
    • B29L2031/756—Microarticles, nanoarticles

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  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Micromachines (AREA)
  • Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
  • Laminated Bodies (AREA)

Abstract

The invention relates to a microfluidic device for rationing liquids into a microfluidic network. The microfluidic channels or chambers are at least partly formed by the introduction of suitable structures into a film above the substrate carrier, so that at least some of the flow of fluid through the network takes place above the plane of the substrate. In order to form a stable channel structure or chamber structure in the film, it is envisaged that in the edge zone between the unattached and attached portions a wedge of material is formed by the viscous flow of the film material as the film is bonded to the substrate, this wedge forming a transition between the chamber wall and the substrate and raising the chamber wall above the plane of the substrate. In one method of producing a finished microfluidic structure a flat planar film is laminated onto a flat sheet-like substrate. During the lamination a mask having at least one recess or opening is pressed onto the film and onto the substrate under pressure and/or under the effect of heat. The film is thereby brought to a temperature at which there is a viscous flow of film and/or substrate medium into the region of the recess or opening, so that a wedge of material is formed and the film bulges up in the region of the recess to form a chamber. The invention further relates to methods of metering at least one liquid in a microfluidic network, in which a capillary stop is overcome by actuating the film, the film being wetted as the capillary stop is removed.

Description

The microfluid foil construction that is used for the rationing fluid
Technical field
The present invention relates to according to the structure of the fluid that is used for the rationing microfluidic networks of aforementioned clause claim 1 and be used to the method making the method for this structure and use this structure rationing fluid.
The present invention is specifically related to those microfluidic structures and devices of utilizing capillary effect or pressure differential transmission fluid, and wherein at least some microfluidic structures are made of chamber and/or the passage that the paper tinsel on the tabular substrate forms.
Background technology
Valve arrangement is known in the prior art, and wherein elastic film is used to open and/or close microfluidic valve.
Therefore, US 2005/0205816 A1 discloses a kind of valve that is used for microfluidic structures, is specifically used for controlling the valve that flows in the microfluidic channel, wherein can interrupt flowing by the fexible film on the flow channel that is arranged on part.Therefore for this purpose, compressed air is applied to the chamber of adjacent films, and film is bent and makes its admission passage path and it is closed.
US 5,811, and 291 have described a kind of microfluidic device of making by stacked two polymer foil (particularly PE paper tinsel) that abut against each other.Because these paper tinsels of effect of pressure and heat are partly connected together and make and can form chamber and passage by the introducing fluid in the lamination area that is not connected.US 5,811, and 291 are specifically related to a kind of test tube.
US 2006/0076068 A1 discloses a kind of micro-fluid pump and a kind of microfluidic valve and their manufacture method, and wherein valve is formed by the film that covers the channel design in the carrier material.Utilize the stacked manufacturing valve of selectivity, and film keeps in the valve zone not attaching.
US 2006/0057030 A1 discloses a kind of microfluidic device, a kind of so-called MEMS device that is used for from the storage pool transmitting fluid, and wherein the fluid storage pond is formed in the substrate plate.Have storage pool and covered by first polymer film as the substrate plate of the passage of fluid-conveying structure.First polymer film has the opening to storage pool and passage.
In addition, second polymer film is arranged on first polymeric films, and this second film is the part arch, makes the chamber by convexing to form.These chambeies fluid are each other separated and are filled gas, when applying sufficient pressurising force, for example the chamber are pressed into together, cause burble point between first film and second film to be opened and compressed air is escaped so that fluid is transferred to passage from storage pool by opening.
US 6,902, and 706 B1 disclose a kind of valve that is used for the fluid of control analysis chip (analysis chip).This valve comprises the paper tinsel of the channel end in the covered substrate.Paper tinsel is the arch projection in the channel end zone, and connects these ends by this arch chamber.Can reduce vault by pneumatic taper driver, thus shut off valve.
US 2005/0037471 A1 discloses a kind of first passage and has been formed on the microfluidic valve in the smooth flexible plastic sheet or the manufacture method of micro-fluid pump.Second instrument is in order to form the second channel in second elastomer layer.On first smooth plane surface that is positioned over the second layer with channel side and attach thereon.Plate that will be lower for example is placed on the smooth flat carrier substrate such as sheet glass then, and second channel is still opened.Fluid by first passage delivery can make the film of the resilient separation material formation at the place, crosspoint between first passage and the second channel can be bent and use as valve thus.
US 2005/02058816 A1 discloses a kind of microfluidic membranes valve, uses the fexible film that is arranged on the flow channel.By introduce air pressure or vacuum in the chamber of adjacent films, film is bent and closes or open flow channel.
In order to obtain according to above-mentioned disclosed valve arrangement or rationing element, general program is can be by making the distortion of elastic foil or flexible plastic sheet to form channel design.
Therefore shortcoming is the profile (contour) that must will form with the high accuracy manufacturing in molded punch die.The cost of punch die (die) of making this three-dimensional microstructuresization is very high.
In addition, the Machining Technology that is used to make this punch die can only be used to be low to moderate the structure of a certain minimum dimension at present.Structure much smaller than 1 micron-scale needs the light technical method to make punch die, and it has further increased the cost of punch die.
Summary of the invention
So microfluidic structures that an object of the present invention is to provide a kind of manufacture method and can be made economically according to this manufacture method.
Another object of the present invention provides the optional method of the microfluidic structures of the dimensional structure of making the micrometer range with nanometer range or one digit number, to make this structure with improved flow behavior.
According to prior art, valve is formed by element usually, and wherein elastic film rests on the fluid-conveying structure of substrate carrier and with relaxed state and closes these flow channels.
Apply pressure to the valve element by applying internal pressure to fluid or outside, film is bent and opens this flow path.
The also known fluid network that forms fluid-conveying structure and will so obtain in the flexure strip material is placed on the flat substrate.In order to drive and control these passages in the target mode, for example one or more channel systems are stacked mutually and by pneumatic or hydraulic dilatation, open or close the passage in another plane thus.Usually, need the structured techniques of effort and costliness so that this fluid network to be provided.
With respect to this background technology, target provides the straightforward procedure of making this structure, and it is without any need for substrate, the pre-structuring of paper tinsel or film, and can the simple working step realize the fluid valve that will make.
Another object of the present invention is the driving of simplifying such as the microfluidic control member of valve, has the passive microfluidic control element of improved fluid transmission characteristic with manufacturing.
By microfluidic structures element,, and realize above purpose according to the method with this microfluidic structures rationing fluid of claim 37 according to the method for this microfluidic structures of manufacturing of claim 13 according to claim 1.
Imagine smooth paper tinsel or film according to the present invention and should be applied to smooth substrate or carrier, more specifically be sealed to this carrier.
Realize sealing by placing stacked carrier and film, stacked particularly.Then for stacked, mask (punch die of heating) is placed on the film.Fluted or the opening of overthrusting mould; In this groove or open area, do not contact between mask (punch die) and the film.
Owing to the pressure that contacts of effect of heating and punch die, film and/or baseplate material begin to flow and this material moves into groove and/or opening.
As a result, in the inward flange zone of groove or opening, material is accumulated with the wedge shape form between substrate and film.
Speech among the present invention " wedge " is meant the accumulation or the accumulation of the film and/or the baseplate material of the fringe region on the not stator between film and the substrate.This shape may be different with the letter of wedge shape, and wedge of material can adopt pearl shape (bead), triangle, circle to cut the combination of shape, ellipse and these shapes or the form in cross section as a result.
If the use multilayer film, this advantageously has the outside materials with high melting point as the low melting point plastic material of the sealant of substrate inboard and cover layer/coverlay form.The diaphragm seal material for example can be ethylene acetate (ethylene vinyl acetate, EVA) or ethylene acrylic (ethylene acrylic acid, EAA), and the material that is used for coverlay is typically polypropylene (PP), perhaps polystyrene, Merlon, polyethylene or acrylates.
Favourable, EVA is in evenly fusing during cascade.This have low viscous material and be pressed in the interval of the mask below the film between melting stage, form pearl shape thing or wedge and also make film protrude into the projection of the film in opening and/or the stable open area.
Fringe region between standing part and non-fixed portions, wedge of material promotes film from base plan.
Favourable, have 60 ℃ to 190 ℃, particularly the plastic material of 85 ℃ to 130 ℃ melting temperature is used for sealant.
The fusion temperature of uniting the cover layer of use or coverlay with sealant should be different from this and also should be higher than this.
Therefore the coverlay material should reach 150 ℃ to 400 ℃, particularly 200 ℃ to 300 ℃ fusion temperature.
In order to realize bonding or crosslinked (cross-linking) of plastics, all fusings.Optionally, if sealant also is sufficient at 60 ℃ to 190 ℃ (more particularly 85 ℃ to 130 ℃) softening down also crosslinked this softener material.Because the crosslinked or bonding of coverlay also may take place in material softening under above-mentioned state of temperature.
The viscosity that depends on the plastics of use does not melt or glutinous formed material also can take place stacked.Film is heated up to membrane material softening, and it flows in the viscosity mode subsequently.
Optionally, also can be stacked by using solvent to carry out.Solvent is applied to the zone of the substrate that will be attached.For selectivity applies, solvent for example can pass through mask injected or brushing or impression.
Subsequently stacked film is positioned over the top and pushes by other mask or punch die.This attaching also can be carried out under the environment temperature that does not apply any heat.In this embodiment, preferred stacked preformed film.The material that begins to dissolve owing to solvent is pressed into the preformed cavity region of film and forms wedge of material.
In the present invention, speech " chamber " is meant any fluid-conveying structure of three-dimensional, such as leading to the valve or the circuit of bag (pouch), elongated passage.The fluid that uses can be fluid and gas.
Favourable, level and smooth flat substrate is used as the substrate of microfluidic device.Substrate or substrate also can be formed by film.Microfluidic structures is only formed by the chamber subsequently, entrance cavity, sample chamber, ratio chamber (ratiochamber) and passage particularly, and it forms the three-dimensional structure in the film and is thus lifted on the not structurized base plan.
Chamber and passage form the complete microfluidic networks on the substrate surface.
Favourable, but the fluid-conveying structure in the substrate also the chamber in the tunicle (such as channel part or the opening in the substrate particularly) cover.Opening in the substrate can be connected to the fluid network of the top and the bottom of substrate, or the opening that passes in its substrate that can be introduced into microfluidic networks by sample fluid is formed into port area.
Opening mouth in the substrate or channel end end at substrate surface and, because opening or passage extend into substrate, the chamber that is positioned at the film on the base plan is formed step.
In the microfluidic device by the device for demonstrating capillarity operation, this step can form capillary to be stoped.
According to the present invention, this capillary stops and can be overcome actively or passively.For this reason, must be wetting at the bottom of chamber wall or the chamber by the step of substrate.
Chamber in the film or channel design are thus lifted to more than the base plan in domed form (more specifically arch) mode.
Fringe region between at the bottom of chamber wall and the chamber forms 2 ° to 90 ° angle, favourable 5 ° to 25 ° angle particularly.Because the angle, small-bore, shallow gap is formed on the edge in chamber.This shallow clearance height of bottom section in the chamber produces high capillary force.
In order to realize passive the overcoming of capillary prevention, the outward flange in chamber is set on the step edge of cross-section hole or channel end, make between the chamber wall of step edge and covering step edge, to stay 1 micron to 50 microns, more specifically 10 microns to 50 microns capillary gap.During operation, this capillary gap can be overcome by the fluid leading peak of building up at the step place and protrude.
In another embodiment, not shown, the capillary prevention is formed by hydrophobic region.This capillary for example stops and can produce by using hydrophobic plastic or coating.This capillary prevention also can be overcome by wetting adjacent membranous wall.
In one embodiment of the invention, film (membrane) is set between film and the substrate.Separation or filtration for the sample fluid that realizes providing for example can be provided this film.Favourable, film for example be set in the through-flow openings of substrate or on, or be set in the supply chamber of the sample fluid that atmosphere is opened.
Film can be set in the gap between film and the substrate particularly, makes film can the bridge joint capillary stop and as wetting auxiliary.
Stop by on step, can initiatively overcoming capillary by press mold downwards, make the capillary gap be lowered to the point that begins wetting chamber from the fluid-conveying structure of substrate.
Favourable, this structure can be used as valve, and the through-flow openings of passing substrate is covered by the chamber.The capillary that is formed by through-flow openings stops the fluid that suppresses opening part to flow.
If subsequently in the zone in chamber, film (that is, the chamber wall on the through-flow openings) is depressed, and then can continue by the wetting this fluid stream that takes place.The elastic cavity wall is therefore as the reversible elasticity opening valve in the microfluidic networks.Because its resilience size stability, membrane material is got back to its home position, in case the fluid of first dosage of feasible rationing flows out, the fluid of dosage also can be by rationing in addition.
In one embodiment of the invention, film is laminated to the top and the bottom of substrate and covers microfluidic structures there or form the miniflow body cavity.
Replacement punch die or drift or other make the film distortion with wetting electromechanical means by pushing the chamber wall downwards, also can be by introducing compressed air or passing through curved substrate rationing fluid.
For this purpose, elastic base plate on substrate carrier contact point or the one or both sides at guiding piece place are clamped and subsequently by mechanical bend.When substrate had forward bending and/or curvature, (deformation-neutral core fibre) compared with substrate deformation neutral core fiber, and the surface is stretched, and film also is stretched as a result.
This has guaranteed that the chamber wall moves with respect to the capillary step, thereby causes wetting.At crooked larger part, passage or chamber can be fully closed.
In auxiliary capacity, substrate also can have the groove of wedge shape particularly or excision portion form in the substrate-side away from film.When curved substrate, obtain high bending radius in these zones, move thereby produce special adjustment highly for the chamber wall.
Favourable, it is thereon supported or as removable punch die and therefore bending is introduced the support member (anvil particularly) of substrate carrier to be arranged on substrate during the bending.
During bending, according to the mathematic sign of bending, it is littler or bigger that the transverse cross-sectional area in passage or chamber becomes.Flowing in passage or the chamber can be had a mind to shrinkage limit by this way.
Can be periodically and carry out the opening and closing in passage or chamber with the direction guidance mode, so the passage of film or chamber are as pump operated.Therefore, for example under the situation in the film chamber that covers two channel ends, expect be at first push chamber wall form downwards by punch die film to close a channel end, move this punch die and force the Fluid Volume of the chamber sealing of opening to enter second channel towards the second channel of still opening is terminal then.
Substitute this pump mechanism, also can utilize the principle of peristaltic pump, wherein drum moves on a direction on the membrane channels.In the linear embodiment of pump, a series of driver of She Zhiing is driven with undulation one by one, and fluid forwards in tubulose elastic membrane passage like this.
Favourable, substrate also can be by flexural vibrations, for example substrate or the intrinsic harmonic resonance (harmonic inherent resonance) that is full of the elastic membrane system of fluid are energized, and make shear wave (vertical wave that particularly moves forward) be pressed into fluid column and therefore drive forwards fluid or help to overcome capillary and stop.
Because the present invention, the chamber that manufacturing has the very little capacity of the volume of 0.01 microlitre, 0.1 microlitre, 0.2 microlitre, 0.5 microlitre, 1 microlitre, 3 microlitres, 5 microlitres, 10 microlitres and 20 microlitres particularly and other volumes is possible, and particularly the chamber of the intermediate sizes that is obtained by the combination of above-mentioned capacity also is possible.
Chamber in the formation film is preferably the dish type cross section, and the cross-sectional width in chamber is at least 20 times of chamber height.
In one embodiment, cross-sectional height is 10 to 15 microns in the cross section apex region, is 5 to 10 microns in the middle transverse cross-sectional area between edge region and peak or the apex region, and is 0.1 micron to 5 microns in the edge region.
If the internal particle of different size (1 to 4 micron blood platelet for example wherein, 7 to 8 microns red blood cell) sample fluid flows that is transmitted is passed the passage with this cross section, then leucocyte is accumulated in the apex region of cross section, and red blood cell is at middle section and the blood platelet fringe region at cross section.
Like this can the separating blood component, particularly when flowing when separated, that is, for example when cross section correspondingly diverges or incorporates the passage of the cross-sectional diameter with association or through-flow openings into.
In one embodiment, the summit or the vault in imagination chamber are lowered.This guarantees to exist in the microfluidic structures high capillary operation, not only in the outer gap zone in film chamber but also at the center in chamber.
Some plastic material can have the ability that changes and recover their shape under fuel factor.
In order to utilize this shape-memory properties, polyethylene film material or polyamide are heated on the so-called activationary temperature, and the shape of expecting under this temperature is presented.Particularly, under this temperature, chamber and/or passage are introduced in the film, particularly by these chambeies are shaped, perhaps particularly by the heated film of hot forming.This film is cooled off fast so that this film keeps the shape of its distortion then.
This film of follow-up heating makes it be returned to its original-shape to being higher than activationary temperature.
By the passage that local heat is handled like this by the shape memory plastic material, this passage can close or open along heating part.
Also can make shut off valve by this way, the chamber is closed via through-flow openings or channel part by it.
With example and diagram form, additional features of the present invention can push away from the following examples.
Description of drawings
In the drawings:
Fig. 1 illustrates the microfluidic structures element in the chamber that has on base plan,
Fig. 2 illustrates the microfluidic structures element with duplicature,
Fig. 3 illustrates the through-flow openings that tunicle covers, and has the capillary step that leads to passage,
Fig. 4 illustrates the microfluidic valve element according to the activation of Fig. 3,
Fig. 5 illustrates the microfluidic channel that is used for the separate out suspended fluid component,
Fig. 6 illustrates the valve element that wherein loose membrane portions covers two channel ends,
Fig. 7 illustrates by the driven valve element of curved substrate,
Fig. 8 illustrates pneumatically-operated valve element,
Fig. 9 and Figure 10 illustrate can be by the pass element on the cross section of the bent-strip of mechanical shrinkage limit,
Figure 11 illustrates the membrane channels during the manufacturing,
Figure 12 illustrates the membrane channels at the center with reduction,
Figure 13 illustrates the membrane channels in the forming tool,
Figure 14 a and Figure 14 b illustrate the membrane channels with sealing and pressure membrane.
The specific embodiment
Fig. 1 illustrates the cross section of the microfluidic structures that is used for rationing and operating fluid.
Microfluidic structures is formed by substrate (1), and substrate (1) comprises breach (breach) or the opening (8) that is well format.
Film (2) attaches at least a portion or the separated region of substrate carrier (1).
In the zone of part that does not attach or not attaching, film protrudes from and makes the membrane portions that does not attach form chamber (6) on the planar substrates surface, forms passage (5) especially on smooth base plan (21).
Membrane portions preferably with fluid tight manner with respect to external environment annular seal space (6).
As the replacement of the opening in the substrate (8) (being specially the inlet opening of microfluidic networks), channel part (5,20) or chamber (6) and valve space also can be delimited in substrate by film, shown in following description.
Advantageously, miniflow body cavity (6) and passage (5) can be formed in the film on the surface of structured substrate not, to avoid and need carry out expensive micro-structural to substrate carrier (1).
In order to make microfluidic device, the substrate that is made of thermoplastic material is at first heated and is cast in the mould (mould), and perhaps the antistructure that goes out mould by coining in mouldable plastics is introduced channel design.Advantageously, have to the not structured substrate sheet on the small part plane and/or smooth surface and can be used for this microfluidic device.The plane of substrate film and/or smooth surf zone can relative to each other be arranged with step or terraced fields form, makes independent surf zone be in different height with respect to the average surface height.
Film is particularly by the stacked surface that is attached to substrate.
Figure 11 illustrates sealing or lamination process, and the smooth not structurized substrate (1) that wherein is made of plastics is supported on to lamination process and forms on the support chip (31) of anti-support.Thermoplastic material film (2) be positioned on this substrate and by heatable pressing mold (pressing die) (31) with pressure P to pressing down.
Baseplate material is preferably by pure polyolefin or polyolefinic mixture, particularly by polyethylene, polypropylene or have propylene or their mixture of the copolymer of ethene constitutes.
For membrane material, the preferred polymer that uses styrene-based/ethylene/butylene, EPR (based on ethene and polyacrylic synthetic rubber), the thermoplastic elastomer (TPE) (TPE) of mixture, EAA or the polypropylene copolymer of EPDM (based on the terpolymer of ethylene propylene diene monomer), polyamide (PA) and polyolefinic alloy (alloy), PP/EPR/PE, PP/EPDM or PE/EVA/EPDM.
Alternatively, also can use PTFE film or PTFE mixture or, be difficult for wetting plastics if adopt with such as the PTFE of fillers such as bronze, glass or carbon as membrane material.
Therefore pressing mold (31) has opening, contacts pressure P and does not put on film on the substrate that is placed in the open area.
Pressing mold (31) is put into the position that is in heated condition and is caused membrane material and/or baseplate material fusing, and word " fusing " is meant that material does not become liquid fully but reached viscosity in the pressure current downflow, or under pressure plastically deformable.
Because stacked (being that material flow to together with crosslinked) depends on pressure and stacked temperature, so these parameters can change in wide region.
Thereby must select pushing surperficial geometry, sealing load, seal temperature and sealing time of pressing mold, make and realize that film (2) attaches to desired intensity and the attaching power on the substrate (1).
If film is removed from mould, should adjust stacked with adhesive strength that 2-5N/10mm is provided easily to remove bonding agent or to provide 5-20N/10mm with more firm attaching bonding agent.
Stacked for what fix, the attaching value of employing 20-80N/10mm, these attaching values are based on the stretching test of adopting the wide dipstick of 10mm.The contact pressure P of using has 0.2-20N/mm under 70 ℃ to 170 ℃ seal temperature 2Value.The sealing time of observing is from 0.2 second to 200 seconds.
Baseplate material has fusion temperature and/or the glass transition temperature higher than membrane material.When execution was stacked in the chosen temperature scope, this caused bigger the softening of membrane material, and membrane material has the fluid ability higher than substrate under stacked condition thereby cause.
Because punch die (31) is exerted pressure P on film (2) and substrate (1), membrane material is concrete owing to lower shear viscosity flows.
Particularly, pressure causes membrane material to be transferred in the zone that does not contact pressure of punch die (31) with shearing force, and forms wedge of material (11) thus in the fringe region of the opening of punch die.
Preferably, the bonding of film (2) and substrate (1) not taking place in the open area of punch die (31), thereby forms not attach area (25).Because flowing of material, material is in attach area projection not and form fluid-conveying structure between substrate and film.These may be as the passage among Figure 11 (5) or chamber (6) or little valve.
The wedge of material (11) that forms impels film in attach area not upwards and the support membrane structure.
Advantageously, film chamber (6) can be arranged on the hole (8) or through-flow (througflow) opening (8) of substrate (1).Since film be flexible it can easily be out of shape, consequently can control in the substrate channel (5) or flowing of passing through-flow openings (8) between the top and bottom of substrate.
As Fig. 1 as can be seen, film chamber (6) can seal by the zone (24) of stacked attaching, so that it is to external world for the liquid sealing.
The shape of film chamber (5) or membrane channels (5) had both depended on the stacked situation of membrane material, such as pressure, stacked time and temperature, depended on the geometry of pressing mold (31) again.
Figure 12 illustrates lamination process, has wherein used the pressing mold (31) of the opening with different size.In less dexter open area and in the bigger grooved area that is being arranged in pressing mold (31) centre, film (2) raises up and wedge of material (11) is formed.
In the central area, projection causes the wave-shaped cross-section of film (2) with respect to substrate (1), forms two passages (5) thus.Advantageously, this wave structure can be used as the central area that protrudes into through-flow openings (8) (centre zone) of film (2) in the zone of through-flow openings (8), as shown in figure 12, this guarantees to have overcome the capillary obstruction that is formed by opening (8), by the film in (sagging) central area of wetting sinking.
Shown in Figure 13 and 14, advantageously imagining final film chamber should be shaped by pressing mold.For this purpose, pressing mold (31) is being pushed the groove that the surface has semicircle.
In the process of pushing, film (2) raises up up to the surface of its abut groove and has therefore recovered semi-circular shape as shown in figure 13.
Powerful especially displacement with film generation membrane material of sealant.
As shown in Figure 2, this film (2) is made of coverlay (3) and diaphragm seal (4).Diaphragm seal is preferably made by EVA and is had than coverlay (3) and the lower fusing point of substrate (1).
During the heating and the P that exerts pressure, mainly, the diaphragm seal material displacement that has minimum shear viscosity under the stacked temperature of selecting is to attach area (25) not and form wedge (11).The amount of the material of displacement, the degree of convexity of wedge of material and size depend on the stacked time, contact parameters such as pressure and temperature.
Fig. 2,14a and 14b show that being used to after the different sealing time made the lamination process or the sealing technology of fluid passage when temperature keeps constant.
After the first sealing time t1, the membrane structure that is made of diaphragm seal (4) and coverlay (3) protrudes into according to also partly being full of it in the semicircle groove of Figure 14 a.
Material from diaphragm seal (4) is wedge shape (11) accumulation and substrate surface is left in the film lifting.Shown in comparison diagram 14b and Figure 14 a, the material thickness of diaphragm seal (4) reduces with the increase of sealing time.After relatively long sealing time t2, the thickness of diaphragm seal (4) significantly reduces, and material flows into the semicircular cavity of the pressing mold (31) that the epiphragma (3) that now has been covered fills up fully.
According to Figure 14 b, existing probably rounded after sealing time t2 in the initial semi-circular channel (5) of its side (at least in territory, lateral areas and territory, base area) restriction by encapsulant.
Because flowing of the material of diaphragm seal (4), the interval that is formed between coverlay (3) and the substrate (1) can be filled up fully.Advantageously, the fill level from 0.1% to 90% of midfeather (6), particularly advantageously from 0.1% to 30%, more particularly be implemented from 0.1% to 5%.
Capillary force in the fringe region of the size substantial effect channel design (5) of wedge.
Have 1 ° to 10 ° opening angle between the wall of substrate (1) and passage (5), have
5 ° angular aperture (aperture angle) and near leg-of-mutton open cross-section can obtain about 10 microns intermediate altitude or apex height in the wide passage (5) of 250 μ m.
In the wide fringe region of 10 μ m, if there is not wedge (11) to exist, then clearance height will be less than 1 μ m.The marginal gap of this order of magnitude is because its height is low will have powerful capillary effect and will form preposition tip (preshooter), i.e. capillary leading peak before it (capillary fronts).
The existence of wedge (11) advantageously causes these high capillary fringe regions to be filled wittingly, thereby prevents the preposition tip effect do not expected.
Therefore, by the angle in aperture shown in Figure 1 and the height of summit (13), can adjust the film chamber (6) during the manufacturing and the capillary property of membrane channels (5) in the target mode.
Advantageously, the shaping of film chamber (6) can be by the geometric influence of the groove in the punch die (31), also can be by the outlet influence of the punch die (31) in the zone of groove.
Counter-pressure can be applied to outlet, for example by introduce air pressure to manufacturing installation from the outside.Can control the speed of crowing technique by this way.
Fig. 3 and 4 illustrates the microfluidic device of the top and bottom of tunicle covered substrate.The top that passage (5) is formed at substrate (2) and bottom and pass cross-section hole (8) and each other fluid be connected.
Exit on the top of cross-section hole (8) exists edge or step (12).The fluid that passes foot passage and rise in cross-section hole (8) forms the meniscus (meniscus) (9) in the film chamber (6) that protrudes into upper end, cross-section hole.
The film that protrudes from the inside, chamber does not initially contact with the meniscus of fluid.Therefore the capillary of the fluid of rising stops in hole (8) with opposing at the edge in hole (8).
Also can need not step (12) and make this capillary prevention.
Distance between film and the hole wall must make the wetting of structure stop at the edge, that is, exist capillary to stop.
When using elastic membrane, capillary stops and can overcome by film is moved.Like this, fluid can be in a controlled manner by rationing.Stop in order to overcome capillary, push film (2) arch or projection by driver (10) downwards with drift (punch) or piston form, make that generation is wetting from meniscus (9) to membranous wall in through-flow openings (8) zone.If driver (10) is pushed fully downwards, it also can stop the rationing process intentionally, because the film that is depressed (2) closes closed pore (8) along the substrate top and along step, forms sealing.
If driver (9) is retracted, owing to the elastic restoring force of membrane material and/or owing to treat the fluid pressure of fluid measured, open chamber (6).
Various functions can be realized in driven film chamber (6) during the rationing process, promptly open and/or close the valve function in chamber (6) and the throttling function that part is closed by driver (10).Also can obtain pumping function by the control opening and closing.
Replace driver, the shape memory character that also can utilize some plastic material (such as polyethylene or polyamide) is with mobile cavity wall or conduit wall.
For this purpose, plastic material is heated on the concrete activationary temperature during manufacture, and this can finish by lamination process.Thus obtained shape, for example in the aforementioned shapes is frozen by quick cooling.If the follow-up point that is heated to again on the activationary temperature of material, it returns to its original-shape.
Membranous wall with semicircle convex surface then loses its arcuate in shape, for example because forming technology shown in Figure 3 is closed cross-section hole (8).
Also can realize that the displacement of chamber wall stops to overcome capillary by distortion.
Can be by thermode, smooth add that hot die or one or more radiator are local carries out heating.Owing to also can obtain this material for the activationary temperature that is lower than (specifically from 20 ℃ to 40 ℃) in 50 ℃ of scopes, therefore the hot activation by sample material also is possible.For this reason, device is cooled to below the following temperature of activationary temperature, and for example to 25 ℃, for example this activationary temperature is 30 ℃.Be higher than under the temperature of activationary temperature, for example 35 ℃, sample fluid is directed, and activates the distortion of membranous wall thus automatically, opens and closes the microfluid capillary thus and stops and valve.
Since some plastics in the same way with the UV light reaction, this SME also can be activated by the irradiation of UV light.For example by controlled long-range UV laser instrument or by using optical fiber, can be locally coupled go into moving of UV light and activated membrane with the optically-coupled admission passage.
Locate in the cross-section hole (8) according to Fig. 4, possible capillary prevention also can be overcome by passive.For this reason, summit, chamber (13) and chamber wall are manufactured and made from 1 micron to 20 microns capillary gap by three-dimensional, from 3 microns to 10 microns capillary gap, remain on the edge of cross-section hole (8) particularly.
The fluid that upwards flows in cross-section hole (8) forms the meniscus (9) in this capillary of bridge joint gap, and the passive thus capillary of closing stops.
Advantageously, film chamber (6) are arranged towards step edge, make the high capillary force of fringe region in chamber be used to form the capillary bridge joint.Advantageously, transitional region also can be provided with auxiliary wetting by hydrophilic coating.
Manufacturing method according to the invention is specially adapted to make the fluid passage (5) that is positioned on the substrate, and its width is the multiple of channel height.Channel width is at least 5 times of channel height, 10 of channel height to 50 times particularly.
This structure can be referring to Fig. 5.Microfluidic channel (5) preferably has 10 microns height at central area A (13), have the height that has 2 to 5 microns in 5 microns to 10 microns height and the edge region C in neighboring region B.Because the limited vertical range of membrane channels (5), the latter can be used to the separating blood component.When passing channel flow, preferably place regional A such as erythrocytic bigger blood particle, preferably place area B such as hematoblastic medium particle, and little plasma component preferably places zone C.By separating these zones, for example blood constitutent shunting or transfer are entered cross-section hole by the respective openings in the flow region, blood constitutent can be classified, separates or filter.
If film (2) if on defining point do not attach to substrate and this regional fluid is connected to microfluid system, then this structure can be used as microfluidic valve.For example, by the engineering properties of suitable selective membrane, can set certain pressure/volume flow ratio.In addition, flow capacity (fluidic capacity) and storage pool drawing-in system in a controlled manner.
In the valve according to Fig. 6, elastic membrane (2) attaches on the substrate (1) along the plane (21) of substrate.After attaching, elastic membrane (2) is placed on the substrate of attach area (25) not.If fluid is directed with certain pressure subsequently, film (2) is expansion in zone (25), makes that two channel ends (20) fluid connects in substrate.
Use compressed air (30) on film, to apply an additional restoring force.Valve can be opened and closed by compressed air.
Alternatively, in this embodiment, shown in the dotted line among Fig. 6, also can obtain the chamber (6) of projection after making, it makes the end fluid connection each other of passage (5).In this embodiment, the chamber also can be opened or closed by compressed air or punch die.
In according to another embodiment shown in Figure 7, microfluidic device is clamped and direction bending as shown by arrows at contact point (23).Because the bending of foil substrate sub-assembly, or, under situation about being bent upwards, film (2) is raised away from wall-attached surface (25) not and allows fluid to flow and passes,, under reclinate situation, film (2) is stretched and is pressed onto thus not on the attach area (25).Like this, can realize valve, pump or throttling function by bending.Advantageously, in order to locate and to strengthen bending, groove is set in substrate.This is set at and will obtains the some place of maximum deflection radius, and is promptly preferred below the microfluid setting element.
The storage of fluid or powder and to be released in the chip lab (lab-on-a-chip) be important problem.Fluid or powder are sealed and are stored normally favourable respectively from chip.If necessary, container can be applied to chip.
Yet, fluid container is coupled on the running system of chip normally debatable.
As Fig. 8 an embodiment who guides fluid or suspension to enter microfluidic device (chip) is shown.
After container was filled fluid or suspension, container or bubble (28) were sealed by nonproliferation film.Particularly, fluid can be an analyte.Be applied on the diaphragm seal of container (28) from bonding or self-closing layer or film.Container can be stored under this condition.
In order to use container, it is placed in the groove (22) of substrate (1), and adhesive linkage on it (29) realizes that with substrate sealing is bonding.At this attaching or assembly process, container for example uses pin (34) to be opened.Contact and seal opening on chip and the container with chip from adhesive linkage.
At the top of device, passage (5) is formed in the substrate.Pin (34) is the hollow needle in the hole (8) that is fixed in (particularly with bonding agent) substrate.Alternatively, pin (34) can form by inserting moulding or injection mo(u)lding during the moulding of substrate carrier (1) or injection mo(u)lding (injection moulding).
Passage (5) is connected to passage (5) via opening (8) fluid in the film (2).Opening (8) quilt is to gas-permeable and in fact to the impermeable drain valve of aqueous fluids, hydrophobic outlet covering.
Film (2) attaches to substrate by its surface, has the not attach area that is positioned at pin opening and channel end place.Film is not placed in and seals to form on the attach area.By guiding compressed air (30), film is manufactured into and raises up, shown in the dotted line among Fig. 8.Compressed air flows and to pass first hollow needle (34) and enter container and make analyte pass second empty needle (34) and transfer in the passage (5).
Figure 10 illustrates an embodiment, and the volume flow (volume flow) of wherein passing passage is in a controlled manner by shrinkage limit.
Substrate (1) with classification thickness has bigger thickness in the first area.There are inlet (35) and outlet (36) in this zone.Inlet (35) and outlet (36) can be connected to other fluidic structures of microfluidic networks (not shown).Also two passages (5) of tunicle (2) covering are extended in branching into of inlet (35) and outlet (36) in substrate.In adjacent area, the thickness of substrate significantly reduces, as according to shown in the cross section of Fig. 9.The membrane channels (5) that fluid is connected to the passage in the first area is formed in the second area, and these passages are thus lifted on that on the plane for smooth substrate.
The substrate that thickness reduces (1) is placed on the supporting member (26), particularly anvil.This substrate regions can adopt the driver (10) that affacts the substrate end to be bent.As shown in Figure 10, bend tension membrane channels (5), thereby the volume flow in the shrinkage limit membrane channels (5).
Reference number
The 1-substrate
The 2-film
The 3-coverlay
4-seals film
The 5-passage
The 6-chamber
The 7-fluid
8-hole/through-flow openings
The 9-meniscus
The 10-driver
The 11-wedge of material
12-step/edge
The 13-summit
The 15-blood platelet
The 16-red blood cell
17-blood plasma
The 20-channel end
The 21-base plan
22-groove/excision portion
The 23-contact point
The 24-attach area
25-is attach area not
The 26-supporting member
The hydrophobic outlet of 27-
28-container/bubble
29-is from adhesive linkage
30-compressed air
The 31-pressing mold
The 32-gripper shoe
The 33-outlet
The 34-pin
The 35-inlet
The 36-outlet
Claims (according to the modification of the 19th of treaty)
1. microfluidic structures, comprise that substrate (1) and smooth attaching to have the film (2) that does not attach this substrate (1) of part (25), making chamber (6) or passage (5) be formed on this does not attach on the base plan (21) of part in (25), it is characterized in that: this film (2) is a multilayer film, be specially duplicature, wherein this film (2) comprises the sealant (4) that is arranged on this substrate and is arranged at cover layer (3) on the sealing layer (4), and wherein sealing layer (4) has fusing and/or the softening temperature lower than this cover layer (3), and wherein do not attach part (25) and attach the partly fringe region between (24) at this, the VISCOUS FLOW of wedge of material (11) by the material of this film when this film (2) is bonded to this substrate (1) forms, and this wedge of material (11) formation transition and wall of lifting this chamber between the wall in this chamber and this substrate (1) leave this base plan (21).
2. according to the microfluidic structures of claim 1, it is characterized in that: the softening temperature of sealing layer (4) is 60 ℃ to 200 ℃, 85 ℃ to 110 ℃ particularly, and the softening temperature of this cover layer (3) is 150 ℃ to 350 ℃, 200 ℃ to 300 ℃ particularly.
3. according to the microfluidic structures of claim 1, it is characterized in that: microfluidic networks is formed by this chamber (6) on this base plan and/or this passage (5).
4. according to the microfluidic structures of claim 1, it is characterized in that: the groove (22) of passage (5) form is formed on an end of the channel part (5) that chamber (6) in this substrate (1) and in this film or passage (5) cover this substrate, and the wall of this channel part in this substrate (1) forms the step that leads to the step in this chamber (6) or lead to the passage (5) in this film (2).
5. according to the microfluidic structures of claim 3 or 4, it is characterized in that: this chamber (6) or this passage (5) cover through-flow openings (8), cover the cross-section hole (8) of passing this substrate (1) particularly, and the outward flange of this chamber (6) is arranged on this cross-section hole (8), make and between the wall in this chamber and the edge of this step (12), produce 1 micron to 20 microns, the capillary gap of 3-10 micron particularly, and/or this passage (5) leads to this cross-section hole (8) at top and bottom, and/or this film (2) is set at this top and this bottom of this substrate.
6. according to the microfluidic structures of claim 1, it is characterized in that: this chamber (6) and/or this passage (5) cross section are dish type, be specially spherical segment, the width of this cross section at least 20 times of the height of this cross section and in the fringe region of this cross section between wall and this base plan (21) in this chamber the angle of formation be 1 ° to 20 °, particularly 5 ° to 12 °.
7. according to the microfluidic structures of claim 6, it is characterized in that: the height in this chamber is 10 to 15 microns in first transverse cross-sectional area that the summit (13) in this chamber is located, in second transverse cross-sectional area between this summit (13) and this edge 5-10 μ m, and be that 0.1 μ m is to 5 μ m in the 3rd fringe region, make because different cross-sectional height, the blood flow particle of different size places different flow regions, wherein red blood cell mainly flows into this first area, blood platelet mainly flows into this second area, and blood plasma mainly flows into the 3rd zone.
8. according to the microfluidic structures of claim 6, it is characterized in that: the center (13) of dome of this base plan (21) or vault is lowered with respect to the perimeter, make the distance at center of this base plan (21) and this vault less than the wall of this vault and half of the maximum normal distance between this base plan (21), through-flow openings (8) wherein, cross-section particularly hole (8) be set at below the vault (13) in this chamber and the center of this vault that reduces as the capillary initial point.
9. according to the microfluidic structures of claim 4, it is characterized in that: the edge of this step (12) form capillary and stop, and by driving the wall in this flexible chamber, the gap at interval can be changed and make that this gap is wetted between the wall in this chamber and the edge of this step.
10. according to the microfluidic structures of claim 6, it is characterized in that: at least two channel ends that are formed in this substrate are covered by the chamber of arcuate in shape, and this substrate (1) has the groove (22) in the zone below the film that this does not attach, have particularly at the groove (22) away from the bottom of this substrate of this film, wherein this groove (22) is wedge shape or spherical or hemispheric or rectangle.
11. microfluidic structures according to claim 10, it is characterized in that: this substrate (1) is flexible, can stand bending stress particularly, particularly can be with the reversible manner elastic bending in wedge area, wherein this substrate (1) comprises mechanical gripping means, and wherein this clamping device is guiding piece and contact point (23).
12. microfluidic structures according to claim 1, it is characterized in that: this baseplate material is flexible, wherein this substrate thickness reduces along the part scope of this chamber and/or this passage, make this zone under the bending force that reduces, be out of shape, the fluid cavity in this film or the cross section of fluid passage are changed, and supporting member (26) wherein, anvil particularly, be set at substrate (1) below, be used to support the substrate that this thickness reduces, make this flow channel form and to pass through the controlled shrinkage limit of crooked this structure.
13. particularly according to the manufacture method of the microfluidic structures of aforementioned claim structure, wherein smooth planar film (2) is laminated on the smooth plate shape substrates (1), it is characterized in that: stacked for this, mask (31) with at least one groove (22) or opening is on the film (2) that is pressed against under pressure and/or the fuel factor on this substrate, wherein this film reaches the temperature in the zone that film and/or substrate media VISCOUS FLOW enter this groove or opening at least, makes wedge of material (11) be formed and this film protrudes to form the chamber in this grooved area.
14. method according to claim 13, it is characterized in that: two-layer at least film (2) is laminated on this substrate, and the layer of this film of contiguous this substrate, sealant (4) particularly, have softening point and/or the melting point lower than outside coverlay (3), and during cascade setting near the fusing of sealing film (4) and/or the temperature of softening temperature, wherein this stacked temperature is 70 ℃ to 350 ℃, 120 ℃ to 150 ℃ particularly.
15. the method according to one of claim 31 to 34 is characterized in that: this film (2) adopts the mask and/or the tabular mask (31) of roller die form to be laminated on this substrate (1), and/or the mask of this film by the stacked device form of punch die is laminated on this substrate.

Claims (48)

1. microfluidic structures, comprise substrate (1) and flatly attach to and have the film (2) that does not attach this substrate (1) of part (25), making chamber (6) or passage (5) be formed on this does not attach on the base plan (21) of part in (25), it is characterized in that: do not attach part (25) and attach partly in the fringe region between (24) at this, the VISCOUS FLOW of wedge of material (11) by the material of this film when this film (2) is bonded to this substrate (1) forms, and this wedge of material (11) formation transition and wall of lifting this chamber between the wall in this chamber and this substrate (1) leave this base plan (21).
2. according to the microfluidic structures of claim 1, it is characterized in that: this film (2) is a multilayer film, is specially duplicature.
3. according to the microfluidic structures of claim 2, it is characterized in that: this film (2) comprises the sealant (4) that is arranged on this substrate and is arranged at cover layer (3) on the sealing layer (4).
4. according to the microfluidic structures of claim 3, it is characterized in that: sealing layer (4) has fusing and/or the softening temperature lower than this cover layer (3).
5. according to the microfluidic structures of claim 4, it is characterized in that: the softening temperature of sealing layer (4) is 60 ℃ to 200 ℃, particularly 85 ℃ to 110 ℃.
6. according to the microfluidic structures of claim 4, it is characterized in that: the softening temperature of this cover layer (3) is 150 ℃ to 350 ℃, particularly 200 ℃ to 300 ℃.
7. according to the microfluidic structures of one of aforementioned claim, it is characterized in that: microfluidic networks is formed by this chamber (6) and/or this passage (5) on this base plan.
8. according to the microfluidic structures of one of aforementioned claim, it is characterized in that: the groove (22) of passage (5) form is formed on an end of the channel part (5) that chamber (6) in this substrate (1) and in this film or passage (5) cover this substrate.
9. microfluidic structures according to Claim 8 is characterized in that: the wall of this channel part in this substrate (1) forms the step that leads to the step in this chamber (6) or lead to the passage (5) in this film (2).
10. according to the microfluidic structures of one of claim 7 or 9, it is characterized in that: this chamber (6) or this passage (5) cover through-flow openings (8), particularly, cover the cross-section hole (8) of passing this substrate (1).
11. microfluidic structures according to claim 10, it is characterized in that: the outward flange of this chamber (6) is arranged on this cross-section hole (8), make between the wall in this chamber and the edge of this step (12), to produce 1 micron to 20 microns, particularly the capillary gap of 3-10 micron.
12. the microfluidic structures according to claim 9 or 10 is characterized in that: this passage (5) leads to this cross-section hole (8) at top and bottom.
13. the microfluidic structures according to claim 12 is characterized in that: this film (2) is set at this top and this bottom of this substrate.
14. microfluidic structures according to claim 1 or 2, it is characterized in that: the cross section of this chamber (6) and/or this passage (5) is a dish type, be specially spherical segment, the width of this cross section is at least 20 times of height of this cross section and the angle that forms between the wall in this chamber and this base plan (21) in the fringe region of this cross section be 1 ° to 20 °, particularly 5 ° to 12 °.
15. microfluidic structures according to claim 14, it is characterized in that: the height in this chamber is 10 to 15 microns in first transverse cross-sectional area that the summit (13) in this chamber is located, in second transverse cross-sectional area between this summit (13) and this edge 5-10 μ m, and be that 0.1 μ m is to 5 μ m in the 3rd fringe region, make that the fluid particles of different size places different flow regions owing to different cross-sectional height.
16. the microfluidic structures according to claim 15 is characterized in that: this fluid is a blood.
17. the microfluidic structures according to claim 16 is characterized in that: red blood cell mainly flows into this first area, and blood platelet mainly flows into this second area, and blood plasma mainly flows into the 3rd zone.
18. microfluidic structures according to claim 14, it is characterized in that: the center (13) of dome of this base plan (21) or vault is lowered with respect to the perimeter, makes the distance at center of this base plan (21) and this vault less than the wall of this vault and half of the maximum normal distance between this base plan (21).
19. the microfluidic structures according to claim 19 is characterized in that: passage (5) or through-flow openings (8), cross-section particularly hole (8) be set at below the vault (13) in this chamber and the center of this vault that reduces as the capillary initial point.
20. microfluidic structures according to one of claim 9 to 11, it is characterized in that: the edge of this step (12) form capillary and stop, and by driving the wall in this flexible chamber, the gap at interval can be changed and make that this gap is wetted between the wall in this chamber and the edge of this step.
21. the microfluidic structures according to claim 14 is characterized in that: at least two channel ends that are formed in this substrate are covered by the chamber of arcuate in shape.
22. the microfluidic structures according to claim 21 is characterized in that: this substrate (1) has the groove (22) in the zone below this film that does not attach, has particularly at the groove (22) away from the bottom of this substrate of this film.
23. the microfluidic structures according to claim 22 is characterized in that: this groove (22) is wedge shape or spherical or hemispheric or rectangle.
24. the microfluidic structures according to claim 22 is characterized in that: this substrate (1) is flexible, can stand bending stress particularly, particularly can be with the reversible manner elastic bending in wedge area.
25. the microfluidic structures according to claim 24 is characterized in that: this substrate (1) comprises mechanical gripping means.
26. the microfluidic structures according to claim 25 is characterized in that: this clamping device is guiding piece and contact point (23).
27. the microfluidic structures according to claim 1 or 2 is characterized in that: this baseplate material is flexible.
28. microfluidic structures according to claim 27, it is characterized in that: this substrate thickness reduces along the part scope of this chamber and/or this passage, make this zone under the bending force that reduces, be out of shape, the cross section of fluid cavity in this film or fluid passage is changed.
29. the microfluidic structures according to claim 28 is characterized in that: supporting member (26), anvil particularly, be set at substrate (1) below, be used to support the substrate that this thickness reduces.
30. the microfluidic structures according to claim 28 or 29 is characterized in that: this flow channel forms can be by the controlled shrinkage limit of crooked this structure.
31. particularly according to the manufacture method of the microfluidic structures of aforementioned claim structure, wherein smooth planar film (2) is laminated on the smooth plate shape substrates (1), it is characterized in that: stacked for this, mask (31) with at least one groove (22) or opening is on the film (2) that is pressed against under pressure and/or the fuel factor on this substrate, wherein this film reaches the temperature in the zone that film and/or substrate media VISCOUS FLOW enter this groove or opening at least, makes wedge of material (11) be formed and this film protrudes to form the chamber in this grooved area.
32. the method according to claim 31 is characterized in that: plate-like mask (31) is used.
33. method according to claim 31 or 32, it is characterized in that: two-layer at least film (2) is laminated on this substrate, and the layer of this film of contiguous this substrate, sealant (4) particularly, have softening point and/or the melting point lower, and during cascade setting near the fusing of sealing film (4) and/or the temperature of softening temperature than outside coverlay (3).
34. the method according to claim 33 is characterized in that: be provided with 70 ℃ to 350 ℃, particularly 120 ℃ to 150 ℃ stacked temperature.
35. the method according to one of claim 31 to 34 is characterized in that: this film (2) adopts the mask laminated of roller die form to this substrate (1).
36. the method according to one of claim 31 to 34 is characterized in that: this film passes through the mask laminated of the stacked device form of punch die to this substrate
37. the method for at least a fluid in the rationing microfluidic networks, wherein this network has at least one fluid communication passageways (5) and/or fluid transmission cavity (6), its each be formed by the film (2) that is molded on the base plan, and this passage (5) and/or this chamber (6) that wherein cover through-flow openings or cross-section hole (8) form the capillary prevention, and wherein by activating this film, gap size between the wall in this chamber and this cross-section hole reduces, so that this film is wetted owing to the elimination of capillary prevention.
38. the method according to claim 37 is characterized in that: the top of this chamber (6) or passage uses punch die (10) to be pushed on the direction of this through-flow openings (8) downwards.
39. the method according to claim 38 is characterized in that: the film that is arranged between this film (2) and this substrate (1) is pushed up to this film wetted downwards.
40. the method for at least a fluid in the rationing microfluidic networks, wherein this network has at least one fluid communication passageways (5) and/or fluid transmission cavity (6), its each form by the film that is overmolded on the base plan (21), it is characterized in that: by crooked this substrate (1), the height of this fluid communication passageways (5) or this fluid transmission cavity (6) is that part changes at least.
41. the method according to claim 40 is characterized in that: be bent in the zone of the groove (22) of this substrate (1) in substrate (1).
42. the method according to claim 40 or 41 is characterized in that: by crooked this substrate (1), this cross section is changed, and feasible flow rate of passing this microfluidic structures can be adjusted and this structure is used as shrinkage limit particularly.
43. the method according to claim 40 or 41 is characterized in that: by crooked this substrate (1), the cross section of this fluid-conveying structure is closed, and this structure specifically is used as valve or pump as a result.
44. the method according to claim 40 or 41 is characterized in that: realize the bending of this substrate (1) by the excitation of intrinsic harmonic resonance.
45. the method according to claim 40 or 41 is characterized in that: the bending of this substrate is by the shear wave wetting continuous vertical wave realization of auxiliary this fluid transmission and/or capillary on the direction of propagation particularly.
46. the method for at least a fluid in the rationing microfluidic networks, wherein this network has at least one fluid communication passageways (5) or fluid transmission cavity (6), its each form by the film that is overmolded on the base plan (21), it is characterized in that: this membrane material is heated on the activationary temperature and therefore changes shape, and the SME by material changes shape particularly.
47. the method according to claim 46 is characterized in that: during alteration of form, valve is opened or closed.
48. the method according to claim 46 is characterized in that: passage (5) is opened or closed.
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